In 1974, it was discovered that echinocandin compounds possess excellent antibacterial activity. And then, many semisynthetic echinocandin compounds have been studied for their pharmacologic activities. In 2001, caspofungin was approved by FDA of the United States, which represents the landmark for the research of antifungal medicaments. Caspofungin, the chemical structure of which is shown by Formula 1, represents a broad-spectrum and low-toxic medicament with unique action site:

Caspofungin analogs and the preparation of Caspofungin have been described in WO94/21677, EP620232, WO96/24613, U.S. Pat. No. 5,552,521, WO97/47645, U.S. Pat. No. 5,936,062, WO02/083713, J. Org. Chem., 2007, 72, 2335-2343, CN101792486A, CN 101648994A, WO2010008493A2, US2010168415A1, EP1785432, and WO2010064219A1.
In WO94/21677 and EP 620232, the method for synthesizing and purifying caspofungin has been disclosed, comprising the following steps: Pneumocandin B0 as the starting material reacts with alkyl thiol or aryl thiol, the resulting product is oxidized to obtain the sulfone intermediate, and then the sulfone intermediate reacts with amines in anhydrous non-protonic solvent to obtain caspofungin, which was purified by chromatography.
According to WO96/24613 and US5552521, the primary amide group in Pneumocandin B0 is reduced to amine group (47% of yield), and then the resulting product reacts with thiophenol and ethylenediamine in turn to obtain caspofungin.
In WO97/47645, U.S. Pat. No. 5,936,062 and J. Org. Chem., 2007, 72, 2335-2343, two stereoselective methods for preparing caspofungin from Pneumocandin B0 have been reported. In the first method, phenyl borate is used as protective group, the amide group in Pneumocandin B0 is reduced to amine group, and then the resulting product reacts with thiophenol and ethylenediamine in turn to obtain the caspofungin; in the second method, Pneumocandin B0 as the starting material reacts with thiophenol, the resulting product is protected by phenyl borate, the amide group in Pneumocandin B0 is reduced to amine group, and then the resulting product reacts with ethylenediamine to obtain caspofungin.
In CN101792486A and CN 101648994A, a method has been disclosed, comprising the following steps: Pneumocandin B0 as the starting material reacts with ethylenediamine under the protection of phenyl borate, and then the amide group in the resulting intermediate is reduced to amine group to obtain caspofungin.
In WO02/083713, US2010168415A1, EP1785432, WO2010064219A1, WO2010061219A1, a method has been disclosed, comprising the following steps: the intermediate of Pneumocandin B0 containing cyano is prepared, and then the intermediate is reduced by using hydrogen to obtain caspofungin.
According to WO2010008493A2, Pneumocandin B0 as the starting material reacts with 4-methoxy thiophenol, the resulting product is protected by phenyl borate, the amide group in Pneumocandin B0 is reduced to amine group under the condition of dehydration by 3 A molecular sieve, and then the resulting product reacts with ethylenediamine to obtain caspofungin.
However, for the yield, purity, stability and waste, none of the disclosed methods is the optimal method for industrialization. The cost for industrialization will be greatly increased due to the repeated use of chromatographic column for many times, thus resulting in great amount of waste. Some methods must be conducted under strict anhydrous conditions (such as, dehydration by 3 A molecular sieve). Most of the methods which use thiophenol with odor and high toxicity, are difficult to be operated, harmful to the operator and severely pollute the environment. Additionally, in some of the existing synthetic methods, isomers will be inevitably produced during the preparation of Pneumocandin B0 containing cyano, the stereoselectivity and yield are not high, and expensive metals are used as catalysts, thereby resulting in high cost for industrialization. Therefore, it is urgent to develop a method for preparing caspofungin which is suitable for industrialization.